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The effectiveness of restarted lithium treatment after discontinuation: reviewing the evidence for discontinuation-induced refractoriness


Corresponding author:

Marco P.M. Boks, M.D.

Department of Psychiatry

Rudolf Magnus Institute of Neuroscience

University Medical Centre Utrecht

HP. B.01.206, Heidelberglaan 100

Utrecht 3584 CX

The Netherlands

Fax: +31 887555487




We sought to determine whether the risk of relapse in patients with bipolar disorder is higher after discontinuation and restart of lithium treatment as compared to continuous lithium treatment in these same patients.


We conducted literature searches in the Pubmed, Embase, Cochrane, and PsycINFO databases with cross-reference checks. Relevant data were extracted and pooled for meta-analysis.


Five relevant studies were included for review, of which three studies qualified for the meta-analysis and included a total of 212 analyzed cases. Two studies found lithium to be less effective after discontinuation and reintroduction and three studies found no decreased effectiveness. The pooled odds ratio for the occurrence of one or more relapses after interruption of lithium treatment compared to continuous treatment was 1.40 (95% confidence interval: 0.85–2.31; p = 0.19).


Although studies are scarce, review and meta-analysis of the available literature does not provide convincing evidence that lithium is less effective when treatment is discontinued and restarted, compared to uninterrupted treatment.

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